Fluid infusion methods for ocular disorder treatment

ABSTRACT

Methods of treating ocular disorders are disclosed, such as a method that includes inserting an implant in eye tissue, using a delivery instrument, such that an inlet portion of the implant is in an anterior chamber of an eye and an outlet portion of the implant is in a physiological outflow pathway; removing the delivery instrument from the eye without removing the implant; and conducting fluid comprising a therapeutic substance through the implant and into the physiological outflow pathway. Another method includes inserting an instrument into a physiologic outflow pathway through which aqueous humor drains from an anterior chamber of an eye; separating first and second walls of tissues which comprise the physiologic outflow pathway by injecting a fluid comprising a drug from the instrument while the instrument remains in the physiologic outflow pathway; and withdrawing the instrument following the injection with said fluid remaining within the eye such that the drug has a therapeutic effect on the eye.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation application of U.S. patentapplication Ser. No. 10/384,912, entitled “Fluid Infusion Methods forGlaucoma Treatment,” filed Mar. 7, 2003, now U.S. Pat. No. 7,186,232 B1,issued Mar. 6, 2007, which application claims the priority benefit ofU.S. Provisional Application No. 60/362,405, entitled “Apparatus andCombination Therapy for Treating Glaucoma,” filed Mar. 7, 2002, and U.S.Provisional Application No. 60/363,980, entitled “Means and Proceduresfor Implanting a Glaucoma Shunt,” filed Mar. 14, 2002, the entireties ofwhich are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to reducing intraocular pressure within theanimal eye. More particularly, this invention relates to a treatment ofglaucoma wherein aqueous humor is permitted to flow out of an anteriorchamber of the eye through a surgically implanted pathway. Furthermore,this invention relates to directly dilating Schlemm's canal and/oraqueous collector channels by injecting fluid through the implantedpathway of a stent.

2. Description of the Related Art

A human eye is a specialized sensory organ capable of light receptionand is able to receive visual images. Aqueous humor is a transparentliquid that fills the region between the cornea, at the front of theeye, and the lens. A trabecular meshwork, located in an anterior chamberangle formed between the iris and the cornea, serves as a drainagechannel for aqueous humor from the anterior chamber, which maintains abalanced pressure within the anterior chamber of the eye.

About two percent of people in the United States have glaucoma. Glaucomais a group of eye diseases encompassing a broad spectrum of clinicalpresentations, etiologies, and treatment modalities. Glaucoma causespathological changes in the optic nerve, visible on the optic disk, andit causes corresponding visual field loss, resulting in blindness ifuntreated. Lowering intraocular pressure is the major treatment goal inall glaucomas.

In glaucomas associated with an elevation in eye pressure (intraocularhypertension), the source of resistance to outflow is mainly in thetrabecular meshwork. The tissue of the trabecular meshwork allows theaqueous humor (hereinafter referred to as “aqueous”) to enter Schlemm'scanal, which then empties into aqueous collector channels in theposterior wall of Schlemm's canal and then into aqueous veins, whichform the episcleral venous system. Aqueous is continuously secreted by aciliary body around the lens, so there is a constant flow of aqueousfrom the ciliary body to the anterior chamber of the eye. Pressurewithin the eye is determined by a balance between the production ofaqueous and its exit through the trabecular meshwork (major route) anduveoscleral outflow (minor route). The portion of the trabecularmeshwork adjacent to Schlemm's canal (the juxtacanilicular meshwork)causes most of the resistance to aqueous outflow.

Glaucoma is broadly classified into two categories: closed-angleglaucoma, also known as angle closure glaucoma, and open-angle glaucoma.Closed-angle glaucoma is caused by closure of the anterior chamber angleby contact between the iris and the inner surface of the trabecularmeshwork. Closure of this anatomical angle prevents normal drainage ofaqueous from the anterior chamber of the eye. Open-angle glaucoma is anyglaucoma in which the exit of aqueous through the trabecular meshwork isdiminished while the angle of the anterior chamber remains open. Formost cases of open-angle glaucoma, the exact cause of diminishedfiltration is unknown. Primary open-angle glaucoma is the most common ofthe glaucomas, and is often asymptomatic in the early to moderatelyadvanced stages of glaucoma. Patients may suffer substantial,irreversible vision loss prior to diagnosis and treatment. However,there are secondary open-angle glaucomas that may include edema orswelling of the trabecular spaces (e.g., from corticosteroid use),abnormal pigment dispersion, or diseases such as hyperthyroidism thatproduce vascular congestion.

All current therapies for glaucoma are directed toward decreasingintraocular pressure. Currently recognized categories of drug therapyfor glaucoma include: (1) Miotics (e.g., pilocarpine, carbachol, andacetylcholinesterase inhibitors), (2) Sympathomimetics (e.g.,epinephrine and dipivalylepinephxine), (3) Beta-blockers (e.g.,betaxolol, levobunolol and timolol), (4) Carbonic anhydrase inhibitors(e.g., acetazolamide, methazolamide and ethoxzolamide), and (5)Prostaglandins (e.g., metabolite derivatives of arachindonic acid).Medical therapy includes topical ophthalmic drops or oral medicationsthat reduce the production of aqueous or increase the outflow ofaqueous. However, drug therapies for glaucoma are sometimes associatedwith significant side effects. The most frequent and perhaps mostserious drawback to drug therapy is that patients, especially theelderly, often fail to correctly self-medicate. Such patients forget totake their medication at the appropriate times or else administer eyedrops improperly, resulting in under- or overdosing. Because the effectsof glaucoma are irreversible, when patients dose improperly, allowingocular concentrations to drop below appropriate therapeutic levels,further permanent damage to vision occurs. Furthermore, current drugtherapies are targeted to be deposited directly into the ciliary bodywhere the aqueous is produced. And, current therapies do not provide fora continuous slow-release of the drug. When drug therapy fails, surgicaltherapy is pursued.

Surgical therapy for open-angle glaucoma consists of lasertrabeculoplasty, trabeculectomy, and implantation of aqueous shuntsafter failure of trabeculectomy or if trabeculectomy is unlikely tosucceed. Trabeculectomy is a major surgery that is widely used and isaugmented with topically applied anticancer drugs, such as 5-flurouracilor mitomycin-C to decrease scarring and increase the likelihood ofsurgical success.

Approximately 100,000 trabeculectomies are performed on Medicare-agepatients per year in the United States. This number would likelyincrease if ocular morbidity associated with trabeculectomy could bedecreased. The current morbidity associated with trabeculectomy consistsof failure (10-15%); infection (a life long risk of 2-5%); choroidalhemorrhage, a severe internal hemorrhage from low intraocular pressure,resulting in visual loss (1%); cataract formation; and hypotonymaculopathy (potentially reversible visual loss from low intraocularpressure). For these reasons, surgeons have tried for decades to developa workable surgery for the trabecular meshwork.

The surgical techniques that have been tried and practiced aregoniotomy/trabeculotomy and other mechanical disruptions of thetrabecular meshwork, such as trabeculopuncture, goniophotoablation,laser trabecular ablation, and goniocurretage. These are all majoroperations and are briefly described below.

Goniotomy and trabeculotomy are simple and directed techniques ofmicrosurgical dissection with mechanical disruption of the trabecularmeshwork. These initially had early favorable responses in the treatmentof open-angle glaucoma. However, long-term review of surgical resultsshowed only limited success in adults. In retrospect, these proceduresprobably failed due to cellular repair and fibrosis mechanisms and aprocess of “filling in.” Filling in is a detrimental effect ofcollapsing and closing in of the created opening in the trabecularmeshwork. Once the created openings close, the pressure builds back upand the surgery fails.

Q-switched Neodynium (Nd) YAG lasers also have been investigated as anoptically invasive trabeculopuncture technique for creatingfull-thickness holes in trabecular meshwork. However, the relativelysmall hole created by this trabeculopuncture technique exhibits afilling-in effect and fails.

Goniophotoablation is disclosed by Berlin in U.S. Pat. No. 4,846,172 andinvolves the use of an excimer laser to treat glaucoma by ablating thetrabecular meshwork. This method did not succeed in a clinical trial.Hill et al. used an Erbium YAG laser to create full-thickness holesthrough trabecular meshwork (Hill et al., Lasers in Surgery and Medicine11:341346, 1991). This laser trabecular ablation technique wasinvestigated in a primate model and a limited human clinical trial atthe University of California, Irvine. Although ocular morbidity was zeroin both trials, success rates did not warrant further human trials.Failure was again from filling in of surgically created defects in thetrabecular meshwork by repair mechanisms. Neither of these is a viablesurgical technique for the treatment of glaucoma.

Goniocurretage is an “ab interno” (from the inside), mechanicallydisruptive technique that uses an instrument similar to a cyclodialysisspatula with a microcurrette at the tip. Initial results were similar totrabeculotomy: it failed due to repair mechanisms and a process offilling in.

Although trabeculectomy is the most commonly performed filteringsurgery, viscocanalostomy (VC) and nonpenetrating trabeculectomy (NPT)are two new variations of filtering surgery. These are “ab externo”(from the outside), major ocular procedures in which Schlemm's canal issurgically exposed by making a large and very deep scleral flap. In theVC procedure, Schlemm's canal is cannulated and viscoelastic substanceinjected (which dilates Schlemm's canal and the aqueous collectorchannels). In the NPT procedure, the inner wall of Schlemm's canal isstripped off after surgically exposing the canal.

Trabeculectomy, VC, and NPT involve the formation of an opening or holeunder the conjunctiva and scleral flap into the anterior chamber, suchthat aqueous is drained onto the surface of the eye or into the tissueslocated within the lateral wall of the eye. These surgical operationsare major procedures with significant ocular morbidity. Whentrabeculectomy, VC, and NPT are thought to have a low chance forsuccess, a number of implantable drainage devices have been used toensure that the desired filtration and outflow of aqueous through thesurgical opening will continue. The risk of placing a glaucoma drainagedevice also includes hemorrhage, infection, and diplopia (doublevision).

All of the above embodiments and variations thereof have numerousdisadvantages and moderate success rates. They involve substantialtrauma to the eye and require great surgical skill in creating a holethrough the full thickness of the sclera into the subconjunctival space.The procedures are generally performed in an operating room and involvea prolonged recovery time for vision. The complications of existingfiltration surgery have prompted ophthalmic surgeons to find otherapproaches to lowering intraocular pressure.

Because the trabecular meshwork and juxtacanilicular tissue togetherprovide the majority of resistance to the outflow of aqueous, they arelogical targets for surgical removal in the treatment of open-angleglaucoma. In addition, minimal amounts of tissue need be altered andexisting physiologic outflow pathways can be utilized.

As reported in Arch. Ophthalm. (2000) 118:412, glaucoma remains aleading cause of blindness, and filtration surgery remains an effective,important option in controlling glaucoma. However, modifying existingfiltering surgery techniques in any profound way to increase theireffectiveness appears to have reached a dead end. The article furtherstates that the time has come to search for new surgical approaches thatmay provide better and safer care for patients with glaucoma.

What is needed, therefore, is an extended, site-specific treatmentmethod for placing a hollow trabecular microstent ab interno fordiverting aqueous humor in an eye from the anterior chamber intoSchlemm's canal. In some aspect of the present invention, it is provideda method for injecting fluid through the common hollow lumen of themicrostent to therapeutically dilate Schlemm's canal and the aqueouscollector channels.

SUMMARY OF THE INVENTION

A device and methods are provided for improved treatment of intraocularpressure due to glaucoma. A hollow trabecular microstent is adapted forimplantation within a trabecular meshwork of an eye such that aqueoushumor flows controllably from an anterior chamber of the eye toSchlemm's canal, bypassing the trabecular meshwork. The trabecularmicrostent comprises a quantity of pharmaceuticals effective in treatingglaucoma, which are controllably released from the device into cells ofthe trabecular meshwork and/or Schlemm's canal. Depending upon thespecific treatment contemplated, pharmaceuticals may be utilized inconjunction with the trabecular microstent such that aqueous flow eitherincreases or decreases as desired. Placement of the trabecularmicrostent within the eye and incorporation, and eventual release, of aproven pharmaceutical glaucoma therapy will reduce, inhibit or slow theeffects of glaucoma.

One aspect of the invention provides an axisymmetric trabecularmicrostent that is implantable within an eye. The microstent comprisesan inlet section containing at least one lumen and one inlet opening, anoutlet section having at least one lumen that connects to at least oneoutlet opening. In some aspect of the present invention, the microstentfurther comprises a flow-restricting member within the lumen that isconfigured to partially prevent back flow from passing through theflow-restricting member. The microstent further comprises a middlesection that is fixedly attached to the outlet section having at leastone lumen in fluid communication with the lumen of the outlet section.The middle section is fixedly attached to the inlet section and thelumen within the middle section is in fluid communication with the lumenof the inlet section. The device is configured to permit fluid enteringthe lumen of the inlet section to pass through the flow-restrictingmember, enter the lumen of the middle section, pass into the lumen ofthe outlet section, and then exit the outlet section.

Another aspect of the invention provides a method of treating glaucoma.The method comprises providing fluid through the lumen of the microstentto therapeutically dilate the aqueous cavity. The term “aqueous cavity”herein refers to any one or more of the downstream aqueous passageways“behind” the trabecular meshwork, including, without limitation,Schlemm's canal, the aqueous collector channels, and episcleral veins.In one embodiment, the fluid contains therapeutic substance, includingpharmaceuticals, genes, growth factors, enzymes and like. In anotherembodiment, the fluid contains sterile saline, viscoelastic, or thelike. The mode of fluid injection may be a pulsed mode, an intermittentmode or a programmed mode. In one aspect, the pressure of the fluidtherapy is effective to cause therapeutic effects on the tissue of theaqueous cavity. In another aspect, the fluid pressure is effective tocause the dilation of the aqueous cavity beyond the tissue elastic yieldpoint for permanent (i.e., plastic) deformation. In other embodiment,the fluid is at an elevated pressure effective to cause plasticdeformation for at least a portion of the aqueous cavity.

Another aspect of the invention provides an apparatus for implanting atrabecular microstent within an eye and dilating the aqueous cavity. Theapparatus comprises a syringe portion and a cannula portion that hasproximal and distal ends. The proximal end of the cannula portion isattached to the syringe portion. The cannula portion further comprises afirst lumen and at least one irrigating hole disposed between theproximal and distal ends of the cannula portion. The irrigating hole isin fluid communication with the lumen. The apparatus further includes aholder including a second lumen for holding the trabecular microstent. Adistal end of the second lumen opens to the distal end of the cannulaportion, and a proximal end of the second lumen is separated from thefirst lumen of the cannula portion. The holder holds the trabecularmicrostent during implantation of the device within the eye, and theholder releases the trabecular microstent when a practitioner activatesdeployment of the device.

Another aspect of the invention provides a method of implanting atrabecular microstent within an eye. The method comprises creating afirst incision in a cornea on a first side of the eye, wherein the firstincision passes through the cornea into an anterior chamber of the eye.The method further comprises passing an incising device through thefirst incision and moving a distal end of the incising device across theanterior chamber to a trabecular meshwork residing on a second side ofthe eye, and using the incising device to create a second incision. Thesecond incision is in the trabecular meshwork, passing from the anteriorchamber through the trabecular meshwork into a Schlemm's canal. Themethod further comprises inserting the trabecular microstent into adistal space of a delivery applicator. The delivery applicator comprisesa cannula portion having a distal end and a proximal end attached to asyringe portion. The cannula portion has at least one lumen and at leastone irrigating hole disposed between proximal and distal ends of thecannula portion. The irrigating hole is in fluid communication with thelumen. The distal space comprises a holder that holds the trabecularmicrostent during delivery and releases the trabecular microstent when apractitioner activates deployment of the device. The method furthercomprises advancing the cannula portion and the trabecular microstentthrough the first incision, across the anterior chamber and into thesecond incision, wherein an outlet section of the trabecular microstentis implanted into Schlemm's canal while an inlet section of thetrabecular microstent remains in fluid communication with the anteriorchamber. The method still further comprises releasing the trabecularmicrostent from the holder of the delivery applicator.

One aspect of the invention includes a method of treating glaucoma,including inserting a stent through an incision in an eye; the stenthaving an inflow portion that is in fluid communication with an outflowportion of the stent; transporting the stent from the incision throughthe anterior chamber of the eye to an aqueous cavity of the eye, suchthat the inflow portion of the stent is positioned in the anteriorchamber and the outflow portion of the stent is positioned at theaqueous cavity; and infusing fluid from the inflow portion to theoutflow portion of the stent.

Some embodiments further include closing the incision, leaving the stentin the eye such that the inflow portion of the stent is positioned inthe anterior chamber of the eye and the outflow portion of the stent ispositioned in Schlemm's canal.

Some embodiments further include positioning the stent such that fluidcommunicating from the inflow portion to the outflow portion of thestent bypasses the trabecular meshwork of the eye.

In some embodiments fluid is infused through a lumen of the stent. Insome embodiments the aqueous cavity is Schlemm's canal. In otherembodiments the aqueous cavity is an aqueous collector channel.

In some embodiments, the infusing further comprises injecting the fluidin at least one of a pulsed mode, an intermittent mode, and a programmedmode.

In some embodiments the infusing of fluid is at a pressure sufficient tocause plastic deformation of at least a portion of the aqueous cavity.

In a preferred arrangement, the fluid is at least one of a salt solutionor viscoelastic.

In some arrangements the infusing further comprises coupling the inflowportion of the stent with a fluid delivery element that transmits thefluid to the stent. In an embodiment the coupling comprises securing ascrew thread arrangement of the fluid delivery element with a receivingthread arrangement of the stent.

In certain preferred arrangements, the fluid comprises a therapeuticsubstance such as a pharmaceutical, a gene, a growth factor, and/or anenzyme.

In other preferred arrangements, the fluid comprises the fluid comprisesa therapeutic substance such as an antiglaucoma drug, a beta-adrenergicantagonist, a TGF-beta compound, and/or an antibiotic.

Some embodiments provide that a temperature of the fluid is raisedsufficiently to enhance the plastic deformation. And some embodimentsprovide that a pH of the fluid is adjusted sufficiently to enhance theplastic deformation.

In some arrangements the method further includes vibrating a tissue ofthe eye.

One aspect of the invention includes a method of treating glaucoma,including inserting a stent through an incision in an eye; the stenthaving an inflow portion that is in fluid communication with an outflowportion of the stent; positioning the stent such that the inflow portionof the stent is positioned in the anterior chamber of the eye and theoutflow portion of the stent is positioned at an aqueous cavity; andinfusing fluid from the inflow portion to the outflow portion of thestent.

In some arrangements the aqueous cavity is Schlemm's canal. In certainarrangements, the method further comprises positioning the stent suchthat the outflow portion of the stent is in Schlemm's canal. In somearrangements the aqueous cavity is an aqueous collector channel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a coronal, cross-sectional view of an eye.

FIG. 2 is an enlarged cross-sectional view of an anterior chamber angleof the eye of FIG. 1.

FIG. 3 is an oblique elevation view of one embodiment of an axisymmetrictrabecular microstent.

FIG. 4 is a detailed view of the proximal section of the microstent ofFIG. 3.

FIG. 5 is an applicator for delivering a microstent and infusing fluidfor therapeutic treatment.

FIG. 6 is an enlarged, cross-sectional view of a preferred method ofimplanting a trabecular microstent within an eye.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The preferred embodiments of the present invention described belowrelate particularly to surgical and therapeutic treatment of glaucomathrough reduction of intraocular pressure. While the description setsforth various embodiment specific details, it will be appreciated thatthe description is illustrative only and should not be construed in anyway as limiting the invention. Furthermore, various applications of theinvention, and modifications thereto, which may occur to those who areskilled in the art, are also encompassed by the general conceptsdescribed below.

FIG. 1 is a cross-sectional view of an eye 10, while FIG. 2 is aclose-up view showing the relative anatomical locations of a trabecularmeshwork 21, an anterior chamber 20, and a Schlemm's canal 22. A sclera11 is a thick collagenous tissue that covers the entire eye 10 except aportion that is covered by a cornea 12. The cornea 12 is a thintransparent tissue that focuses and transmits light into the eye andthrough a pupil 14, which is a circular hole in the center of an iris 13(colored portion of the eye). The cornea 12 merges into the sclera 11 ata juncture referred to as a limbus 15. A ciliary body 16 extends alongthe interior of the sclera 11 and is coextensive with a choroid 17. Thechoroid 17 is a vascular layer of the eye 10, located between the sclera11 and a retina 18. An optic nerve 19 transmits visual information tothe brain and is the anatomic structure that is progressively destroyedby glaucoma.

The anterior chamber 20 of the eye 10, which is bound anteriorly by thecornea 12 and posteriorly by the iris 13 and a lens 26, is filled withaqueous humor (hereinafter referred to as “aqueous”). Aqueous isproduced primarily by the ciliary body 16, then moves anteriorly throughthe pupil 14 and reaches an anterior chamber angle 25, formed betweenthe iris 13 and the cornea 12. In a normal eye, aqueous is removed fromthe anterior chamber 20 through the trabecular meshwork 21. Aqueouspasses through the trabecular meshwork 21 into Schlemm's canal 22 andthereafter through a plurality of aqueous veins 23, which merge withblood-carrying veins, and into systemic venous circulation. Intraocularpressure is maintained by an intricate balance between secretion andoutflow of aqueous in the manner described above. Glaucoma is, in mostcases, characterized by an excessive buildup of aqueous in the anteriorchamber 20, which leads to an increase in intraocular pressure. Fluidsare relatively incompressible, and thus intraocular pressure isdistributed relatively uniformly throughout the eye 10.

As shown in FIG. 2, the trabecular meshwork 21 is adjacent to a smallportion of the sclera 11. Exterior to the sclera 11 is a conjunctiva 24.Traditional procedures that create a hole or opening for implanting adevice through the tissues of the conjunctiva 24 and sclera 11 involveextensive surgery, as compared to surgery for implanting a device, asdescribed herein, which ultimately resides entirely within the confinesof the sclera 11 and cornea 12. A microstent 81 is shown placed throughtrabecular meshwork 21 having a distal portion 83 disposed withinSchlemm's canal 22 and a proximal portion 82 disposed within theanterior chamber 20 of the eye 10. FIG. 6 generally illustrates the useof one embodiment of a trabecular microstent 81 for establishing anoutflow pathway, passing through the trabecular meshwork 21, which isdiscussed in greater detail below.

FIG. 3 illustrates a preferred embodiment of a hollow trabecularmicrostent 81, which facilitates the outflow of aqueous from theanterior chamber 20 into Schlemm's canal 22, and subsequently into theaqueous collectors and the aqueous veins so that intraocular pressure isreduced. In the illustrated embodiment, the trabecular microstent 81comprises an inlet section 82, having an inlet opening 86, a middlesection 84, and an outlet section 83 having at least one opening 87, 88.The middle section 84 may be an extension of, or may be coextensivewith, the inlet section 82. The device 81 comprises at least one lumen85 within section 84, which is in fluid communication with the inletopening 86 and the outlet opening 87, 88, thereby facilitating transferof aqueous through the device 81. In one aspect, the outlet sideopenings 88, each of which is in fluid communication with the lumen 85for transmission of aqueous, are arranged spaced apart around thecircumferential periphery 80 of the outlet section 83. In anotheraspect, the outlet openings 88 are located and configured to enablejet-like infusing fluid impinging any specific region of Schlemm's canaltissue suitably for tissue stimulation.

As will be apparent to a person skilled in the art, the lumen 85 and theremaining body of the outlet section 83 may have a cross-sectional shapethat is oval, circular, or other appropriate shape. Preferably, themiddle section 84 has a length that is roughly equal to a thickness ofthe trabecular meshwork 21, which typically ranges between about 100 μmand about 300 μm.

To further stent or open Schlemm's canal after implanting theaxisymmetric device 81, a plurality of elevated (that is, protrudingaxially) supports or pillars 89 is located at the distal-most end of theoutlet section 83 sized and configured for allowing media (for example,aqueous, liquid, balanced salt solution, viscoelastic fluid, therapeuticagents, or the like) to be transported freely.

The microstent 81 may further comprises a flow-restricting member 90,which is tightly retained within a lumen 85. The flow-restricting member90 serves to selectively restrict at least one component in blood frommoving retrograde, i.e., from the outlet section 83 into the anteriorchamber 20 of the eye 10. Alternatively, the flow-restricting member 90may be situated in any location within the device 81 such that bloodflow is restricted from retrograde motion. The flow-restricting member90 is sized and configured for maintaining the pressure of the infusedfluid within the aqueous cavity for a suitable period of time. Theflow-restricting member 90 may, in other embodiments, be a filter madeof a material selected from the following filter materials: expandedpolytetrafluoroethylene, cellulose, ceramic, glass, Nylon, plastic, andfluorinated material such as polyvinylidene fluoride (“PVDF”) (tradename: Kynar, by DuPont).

The trabecular microstent 81 may be made by molding, thermo-forming, orother micro-machining techniques. The trabecular microstent 81preferably comprises a biocompatible material such that inflammationarising due to irritation between the outer surface of the device 81 andthe surrounding tissue is minimized. Biocompatible materials which maybe used for the device 81 preferably include, but are not limited to,titanium, stainless steel, medical grade silicone, e.g., Silastic™,available from Dow Corning Corporation of Midland, Mich.; andpolyurethane, e.g., Pellethane™, also available from Dow CorningCorporation. In other embodiments, the device 81 may comprise othertypes of biocompatible material, such as, by way of example, polyvinylalcohol, polyvinyl pyrolidone, collagen, heparinized collagen,polytetrafluoroethylene, expanded polytetrafluoroethylene, fluorinatedpolymer, fluorinated elastomer, flexible fused silica, polyolefin,polyester, polysilicon, and/or a mixture of the aforementionedbiocompatible materials, and the like. In another aspect, the microstentis made of a biodegradable material selected from a group consisting ofpoly(lactic acid), polyethylene-vinyl acetate, poly(lactic-co-glycolicacid), poly(D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate),poly(caprolactone), poly(glycolic acid), and copolymer thereof.

In still other embodiments, composite biocompatible material may beused, wherein a surface material may be used in addition to one or moreof the aforementioned materials. For example, such a surface materialmay include polytetrafluoroethylene (PTFE) (such as Teflon™), polyimide,hydrogel, heparin, therapeutic drugs (such as beta-adrenergicantagonists, TGF-beta, and other anti-glaucoma drugs, or antibiotics),and the like.

As is well known in the art, a device coated or loaded with aslow-release substance can have prolonged effects on local tissuesurrounding the device. The slow-release delivery can be designed suchthat an effective amount of substance is released over a desiredduration. “Substance,” as used herein, is defined as any therapeutic oractive drug that can stop, mitigate, slow-down or reverse undesireddisease processes.

In one embodiment, the device 81 may be made of a biodegradable (alsoincluding bioerodible) material admixed with a substance for substanceslow-release into ocular tissues. In another embodiment, polymer filmsmay function as substance containing release devices whereby the polymerfilms may be coupled or secured to the device 81. The polymer films maybe designed to permit the controlled release of the substance at achosen rate and for a selected duration, which may also be episodic orperiodic. Such polymer films may be synthesized such that the substanceis bound to the surface or resides within a pore in the film so that thesubstance is relatively protected from enzymatic attack. The polymerfilms may also be modified to alter their hydrophilicity, hydrophobicityand vulnerability to platelet adhesion and enzymatic attack.

The device 81 may be used for a direct release of pharmaceuticalpreparations into ocular tissues. As discussed above, thepharmaceuticals may be compounded within the device 81 or form a coatingon the device 81. Any known drug therapy for glaucoma may be utilized.

FIG. 4 shows a detailed view of the proximal section 82 of themicrostent 81 of FIG. 3. In some aspect, the proximal section 82 has abottom peripheral surface 91 that is about perpendicular to the lumen 85of the microstent 81. A receiving thread arrangement 95 is appropriatelylocated on the peripheral surface 91. The receiving thread arrangement95 is sized and configured to releasably receive a screw threadarrangement 96 for coupling together, wherein the screw threadarrangement 96 is disposed at the distal end 97 of a fluid deliveryelement 94 which has a lumen 93 for transporting the infusing fluid intothe aqueous cavity for therapeutic purposes. The coupling of thereceiving thread arrangement 95 and the screw thread arrangement 96makes the fluid infusion through the lumen 85 leak-proof enablingpressurized the aqueous cavity.

FIG. 5 shows a distal portion 57 of an applicator 55 for delivering amicrostent 81 and infusing fluid for therapeutic treatment. The distalportion 57 comprises a distal cutting means 42 sharp enough for creatingan incision on the cornea and also creating an opening on trabecularmeshwork 21 for stent placement. The axisymmetric microstent 81 issnugly placed within the lumen 43 of the applicator 55 and retained by aplurality of stent retaining members 45. The microstent 81 is deployedfrom the applicator 55 once the distal section 83 passes beyond the edgeof the trabecular meshwork 21. In one aspect, the stent deployment isfacilitated by a plunger-type deployment mechanism 44 with an associateddeployment actuator 61 mounted on the handle 62 of the applicator 55(see FIG. 6).

The microstent 81 may be releasably coupled with a fluid deliveryelement 94 at any convenient time during the procedures. In one aspect,the screw-unscrew coupling steps between the microstent 81 and the fluiddelivery element 94 is carried out by suitably rotating the fluiddelivery element 94 with reference to the stent receiving threadarrangement 95, wherein the associated rotating mechanism 63 is locatedat the handle 62 of the applicator 55.

As will be appreciated by those of ordinary skill in the art, the device81 may advantageously be practiced with a variety of sizes and shapeswithout departing from the scope of the invention. Depending upon thedistance between the anterior chamber 20 and the drainage vessel (e.g.,a vein) contemplated, the devices 81 may have a length ranging fromabout 0.05 centimeters to over 1 centimeter. Preferably, the device 81has an outside diameter ranging between about 30 μm and about 500 μm,with the lumen 85 having diameters ranging between about 20 μm and about250 μm, respectively. In addition, the device 81 may have a plurality oflumens to facilitate transmission of multiple flows of aqueous orinfusing fluid.

One preferred method for increasing aqueous outflow in the eye 10 of apatient, to reduce intraocular pressure therein, comprises bypassing thetrabecular meshwork 21. In operation, the middle section 84 of thedevice 81 is advantageously placed across the trabecular meshwork 21through a slit or opening. This opening can be created by use of alaser, a knife, thermal energy (radiofrequency, ultrasound, microwave),cryogenic energy, or other surgical cutting instrument. The opening mayadvantageously be substantially horizontal, i.e., extendinglongitudinally in the same direction as the circumference of the limbus15 (FIG. 2). Other opening directions may also be used, as well. Theopening may advantageously be oriented at any angle, relative to thecircumference of the limbus 15, that is appropriate for inserting thedevice 81 through the trabecular meshwork 21 and into Schlemm's canal 22or other outflow pathway, as will be apparent to those skilled in theart. Furthermore, the outlet section 83 may be positioned into fluidcollection channels of the natural outflow pathways. Such naturaloutflow pathways include Schlemm's canal 22, aqueous collector channels,aqueous veins, and episcleral veins.

FIG. 6 generally illustrates a preferred method by which the trabecularmicrostent 81 is implanted within the eye 10. In the illustrated method,a delivery applicator 55 is provided, which preferably comprises asyringe portion 64 and a cannula portion 65, which contains at least onelumen 43 in fluid communication with the fluid supply 66. The cannulaportion 65 preferably has a size of about 30 gauge. However, in otherembodiments, the cannula portion 65 may have a size ranging betweenabout 16 gauges and about 40 gauges. A holder 56 at the distal portion57 of the cannula portion 65 for holding the device 81 mayadvantageously comprise a lumen, a sheath, a clamp, tongs, a space, andthe like.

In the method illustrated in FIG. 6, the device 81 is placed into thelumen 43 of the delivery applicator 55 and then advanced to a desiredimplantation site within the eye 10. The delivery applicator 55 holdsthe device 81 securely during delivery and releases it when thepractitioner initiates deployment actuator 61 of the applicator 55.

In a preferred embodiment of trabecular meshwork surgery, a patient isplaced in a supine position, prepped, draped, and appropriatelyanesthetized. A small incision 52 is then made through the cornea 12with a self-trephining applicator 55. The incision 52 preferably has asurface length less than about 1.0 millimeter in length and mayadvantageously be self-sealing. Through the incision 52, the trabecularmeshwork 21 is accessed, wherein an incision is made with a cuttingmeans 42 enabling forming a hole on the trabecular meshwork 21 for stentplacement. The hole on the trabecular meshwork can also be created witha tip having thermal energy or cryogenic energy. After the device 81 isappropriately implanted, the applicator 55 is withdrawn and thetrabecular meshwork surgery is concluded.

In some aspect of the present invention, it is provided a method forexpanding or attenuating the capacity of the existing canal outflowsystem (also known as the “aqueous cavity”). This system could havebecome constricted or blocked due to age or other factors associatedwith glaucoma. In one aspect, a tight fluid coupling is establishedbetween an external pressured fluid source 66 and Schlemm's canal 22through a microstent 81. It is also advantageous to connect the externalpressurized fluid source through a removable instrument (for example, atemporary applicator, catheter, cannula, or tubing) to Schlemm's canalab interno for applying the fluid infusion therapy.

Once the fluid coupling is established, the pressure in the canal israised by injecting fluid or fluid with therapeutic substances. In someaspect of the present invention, a method is provided of treatingglaucoma including infusing fluid into aqueous cavity from an anteriorchamber end of a stent, wherein the fluid is at an elevated pressureabove a baseline pressure of the aqueous cavity. The method furthercomprises placing a hollow trabecular microstent bypassing thetrabecular meshwork, wherein the fluid is infused from the anteriorchamber through a lumen of the microstent. The mode of fluid injectionis selected from a group consisting of a pulsed mode, an intermittentmode, a programmed mode, or combination thereof. In one aspect, thepressure of the fluid therapy is effective to cause therapeutic effectson the tissue of the aqueous cavity. In another aspect, the fluidpressure is effective to cause the dilation of the aqueous cavity beyondthe tissue elastic yield point for plastic permanent deformation. Inother embodiment, the fluid is at an elevated pressure effective tocause plastic deformation for at least a portion of the aqueous cavity.

The fluid may be a salt solution such as Balanced Salt Solution, aviscoelastic (such as Healon), any other suitable viscous or non-viscousliquid, or suitable liquid loaded with drug at a concentration suitablefor therapeutic purposes without causing safety concerns. A combinationof liquids may also be used. The pressure is raised at an appropriaterate of rise to an appropriate level and for an appropriate length oftime, as determined through development studies, to provide for theexpansion of the outflow structures and/or a clearing of any blockageswithin them. The procedure can be augmented with other aids to enhanceits effectiveness. These aids may include heat, vibration (sonic orultrasonic), pulsation of a pressure front, pH, drugs, etc. It isintended that the aqueous cavity be expanded (attenuation or tissuestimulation) by this procedure resulting in an increased capacity forinflow and outflow of Schlemm's canal.

In some aspect of the present invention, it is provided a method forusing a removable applicator, catheter, cannula, or tubing that isplaced ab interno through the trabecular meshwork into the aqueouscavity of an eye adapted for infusing therapeutic liquid into theaqueous cavity.

In some aspect of the present invention, it is disclosed a method oftreating glaucoma, the method including: providing at least onepharmaceutical substance incorporated into an axisymmetric trabecularmicrostent; implanting the microstent within a trabecular meshwork of aneye such that a first end of the microstent is positioned in an anteriorchamber of the eye while a second end is positioned in a Schlemm'scanal, wherein the first and second ends of the microstent establish afluid communication between the anterior chamber and the Schlemm'scanal; and allowing the microstent to release a quantity of thepharmaceutical substance into the eye. In one embodiment, the methodfurther comprises a step of infusing fluid into the Schlemm's canal fromthe anterior chamber through a lumen of the microstent, wherein thefluid is at an elevated pressure above a baseline pressure of theSchlemm's canal.

Although preferred embodiments of the invention have been described indetail, certain variations and modifications will be apparent to thoseskilled in the art, including embodiments that do not provide all of thefeatures and benefits described herein. Accordingly, the scope of thepresent invention is not to be limited by the illustrations or theforegoing descriptions thereof, but rather solely by reference to theappended claims and their equivalents.

1-20. (canceled)
 21. A method of treating an ocular disorder,comprising: using a delivery instrument to insert an implant in eyetissue such that an inlet portion of the implant is in an anteriorchamber of an eye and an outlet portion of the implant is in aphysiological outflow pathway; removing the delivery instrument from theeye without removing the implant; and conducting fluid comprising atherapeutic substance through the implant and into the physiologicaloutflow pathway.
 22. The method of claim 21, wherein conducting fluidcomprises infusing the therapeutic substance into the inlet portion ofthe implant.
 23. The method of claim 21, wherein conducting fluidcomprises conducting the fluid comprising the therapeutic substance fromthe inlet portion of the implant to the outlet portion of the implant.24. The method of claim 21, wherein the fluid travels through theanterior chamber of the eye to the implant.
 25. The method of claim 24,wherein the fluid travels through a delivery lumen to the implant. 26.The method of claim 25, wherein the delivery lumen is in fluidcommunication with a lumen of the implant.
 27. The method of claim 26,wherein the delivery lumen is coupled to the lumen of the implant. 28.The method of claim 21, wherein the physiological outflow pathwaycomprises an aqueous pathway.
 29. The method of claim 28, wherein thephysiological outflow pathway comprises Schlemm's canal.
 30. The methodof claim 29, wherein the eye tissue comprises trabecular meshwork. 31.The method of claim 21, wherein the therapeutic substance is selectedfrom the group consisting of a pharmaceutical, a gene, a growth factor,and an enzyme.
 32. The method of claim 21, wherein the therapeuticsubstance is selected from the group consisting of an antiglaucoma drug,a beta-adrenergic antagonist, a TGF-beta compound, and an antibiotic.33. A method of treating an ocular disorder, comprising: inserting animplant through an incision in an eye; positioning the implant in theeye such that an inlet portion of the implant is in an anterior chamberof the eye and an outlet portion of the implant is in a physiologicaloutflow pathway with the inlet an outlet portions being in fluidcommunication; providing a delivery lumen such that the delivery lumenis in fluid communication with the implant; and infusing a fluidexternal to the eye through the delivery lumen such that the fluid flowsfrom the inlet portion of the implant to the outlet portion of theimplant and into the physiological outflow pathway.
 34. The method ofclaim 33, wherein the method further comprises using a deliveryinstrument to transport the implant.
 35. The method of claim 34, whereinthe implant is transported through eye tissue.
 36. The method of claim34, wherein the implant is transported through the anterior chamber ofthe eye.
 37. The method of claim 33, wherein providing a delivery lumencomprises coupling the delivery lumen to the inlet portion of theimplant.
 38. The method of claim 33, wherein providing a delivery lumencomprises coupling the delivery lumen to a lumen of the implant suchthat the lumens are in fluid communication.
 39. The method of claim 33,wherein the fluid comprises a drug.
 40. The method of claim 33, whereinthe fluid comprises a therapeutic agent.
 41. The method of claim 33,wherein the fluid comprises a therapeutic substance selected from thegroup consisting of a pharmaceutical, a gene, a growth factor, and anenzyme.
 42. The method of claim 33, wherein the fluid comprises atherapeutic substance selected from the group consisting of anantiglaucoma drug, a beta-adrenergic antagonist, a TGF-beta compound,and an antibiotic.
 43. The method of claim 33, wherein the physiologicaloutflow pathway comprises an aqueous pathway.
 44. The method of claim43, wherein the physiological outflow pathway comprises Schlemm's canal.45. A method of treating an ocular disorder, comprising: inserting aninstrument into a physiologic outflow pathway through which aqueoushumor drains from an anterior chamber of an eye; separating first andsecond walls of tissues which comprise the physiologic outflow pathwayby injecting a fluid comprising a drug from the instrument while theinstrument remains in the physiologic outflow pathway; and withdrawingthe instrument following the injection with said fluid remaining withinthe eye such that the drug has a therapeutic effect on the eye.
 46. Themethod of claim 45 additionally comprising inserting the instrument intothe anterior chamber of the eye and advancing the instrument through eyetissue separating the anterior chamber from the physiologic outflowpathway.
 47. The method of claim 45 additionally comprising contactingscleral tissue with the instrument before separation.
 48. The method ofclaim 45, wherein at least one of the separated tissues is scleraltissue.
 49. The method of claim 48, wherein the fluid comprises atherapeutic substance selected from the group consisting of apharmaceutical, a gene, a growth factor, and an enzyme.
 50. The methodof claim 48, wherein the fluid comprises a therapeutic substanceselected from the group consisting of an antiglaucoma drug, abeta-adrenergic antagonist, a TGF-beta compound, and an antibiotic.